ArticleEuropean journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology2024
In vivo development of resistance to novel β-lactam/β-lactamase inhibitor combinations in KPC-producing Klebsiella pneumoniae infections: a case series.
Article in European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed.
- Caerin 1.1/1.9 Inhibits Growth and Biofilm Formation of Carbapenem-Resistant Klebsiella pneumoniae and Induces Coordinated Transcriptomic Stress Responses.Current microbiology · 2026Article
- Emergence of carbapenemase KPC-14 in anJAC-antimicrobial resistance · 2026Article
- Article
- Novel Insights into Carbapenem Resistance: Mechanisms, Diagnostics, and Future Directions.Antibiotics (Basel, Switzerland) · 2026Review
- In vivo evolution of resistance to novel β-lactam/β-lactamase inhibitor combinations through overproduction of the horizontally acquired extended-spectrum AmpC β-lactamase FOX-14 and porin disruption in Serratia marcescens.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026Article
- Genomic characterization of ceftazidime/avibactam-resistant KPC-producingFrontiers in microbiology · 2026Article
- Rapid and high-sensitivity quantitative fluorescent immunoassay for detection ofFrontiers in microbiology · 2026Article
- Impact of ompK35 and ompK36 downregulation on antibiotic resistance in clinical carbapenem-resistant Klebsiella pneumoniae isolates.Folia microbiologica · 2025Article
- Epidemiology, resistance profiles, and risk factors of multidrug- and carbapenem-resistant Serratia marcescens infections: a retrospective study of 242 cases.BMC infectious diseases · 2025Article
- Aztreonam/avibactam activity against Enterobacterales from European medical centres: summary of 5 years of surveillance prior to approval for clinical use (2019-2023).The Journal of antimicrobial chemotherapy · 2025Article
- Identifying drivers of β-lactam/β-lactamase inhibitor resistance emergence and spread before their clinical deployment.medRxiv : the preprint server for health sciences · 2025Article
- Clinical and Microbiological characteristics of patients with ceftazidime/avibactam-resistant Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae strains.Annals of clinical microbiology and antimicrobials · 2025Article
- Identification of two KPC variants, KPC-204 and KPC-227, in ST11-K64Frontiers in microbiology · 2025Article
- Molecular resistance mechanisms to newly approved antibiotics (2017-2025) in WHO priority pathogens.Frontiers in microbiology · 2025Review
- Updates on the Activity, Efficacy and Emerging Mechanisms of Resistance to Cefiderocol.Current issues in molecular biology · 2024Review
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5 authors.
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Abstract
introductionUnderstanding the dynamics that may characterize the emergence of KPC variants with resistance to novel β-lactam/β-lactamase inhibitor combinations (βL/βLICs) represents a challenge to be overcome in the appropriate use of recently introduced antibiotics.
methodsRetrospective case series describing development of multiple resistance to novel βL/βLICs in patients with KPC-producing Klebsiella pneumoniae (KPC-Kp) infections treated with these drugs. Clinical-microbiological investigation and characterization of longitudinal strains by Whole-Genome Sequencing were performed.
resultsFour patients with KPC-Kp bloodstream infections were included. Most frequent clinical features were kidney disease, obesity, cardiac surgery as reason for admission, ICU stay, treatment with ceftazidime/avibactam, and pneumonia and/or acute kidney injury needing renal replacement therapy as KPC-Kp sepsis-associated complications. The development of resistance to ceftazidime/avibactam was observed in four longitudinal strains (three of which were co-resistant to aztreonam/avibactam and cefiderocol) following treatments with ceftazidime/avibactam (n = 3) or cefiderocol (n = 1). Resistance to meropenem/vaborbactam and imipenem/cilastatin/relebactam was observed in one case after exposure to ceftazidime/avibactam and imipenem/cilastatin/relebactam. Resistome analysis showed that resistance to novel βL/βLICs was related to specific mutations within bla
conclusionTherapy with novel βL/βLICs or cefiderocol may lead to the selection of resistant mutants in the presence of factors influencing the achievement of PK/PD targets. KPC variants are mainly associated with resistance to ceftazidime/avibactam, and some of them (e.g. KPC-14) may also be associated with reduced susceptibility to aztreonam/avibactam and/or cefiderocol. Loss of function of the OmpK35 and OmpK36 porins appears to play a role in the development of resistance to meropenem/vaborbactam and/or imipenem/relebactam, but other mechanisms may also be involved.
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